Promotion of lifespan by mitochondrial Ca2+-induced ROS

In an aging society, we face an increasing number of age-related diseases. Since treatment options are often limited, there is a need for new therapeutic approaches. As cellular power plants, production sites for reactive oxygen species, and triggers of programmed cell death, mitochondria are critical regulators in the aging process, and a proper mitochondrial function is crucial to longevity. For example, small amounts of reactive oxygen species can trigger an adaptation of the mitochondria, associated with a longer lifespan. This process is called mitohormesis. Mitochondrial function is strongly regulated by calcium, which modulates enzyme activity, membrane potential, and the initiation of programmed cell death. To study the interplay between calcium and mitochondrial function, we performed experiments in roundworms (Caenorhabditis elegans). Based on the obtained results, we assume that a specific modulation in mitochondrial calcium uptake triggers mitohormesis and, thereby, lifespan extension. Consequently, we try to answer the following questions: Which proteins can serve as targets for modulating calcium homeostasis? What is the right timing for interventions to extend lifespan and improve fitness? How do mitochondrial calcium modulations alter signals of reactive oxygen species? How does mitochondrial calcium affect mitochondrial metabolism and integrity during aging? To answer these questions, Corina Madreiter-Sokolowski, Associate Professor of "Molecular Aging" at the Medical University of Graz, and her group investigate the impact of mitochondrial calcium modulation on aging, reactive oxygen species, and mitochondrial integrity in roundworms. In addition, they use cellular aging models to test whether results obtained in nematodes can be translated to mammalian cells. The current project aims to combine the know-how of the various aging models with cutting-edge microscopy. The project aims to unveil interventions that counteract the development of age-related diseases and prolong the health span.